APOE: Apolipoprotein E – Genetic Risk Factor in Alzheimer's and Cardiovascular Disease
Comprehensive genomic, proteomic, and clinical annotation of the APOE gene
Gene Information Card
| Symbol | APOE |
|---|---|
| Full Name | Apolipoprotein E |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 348 ncbi.nlm.nih.gov/gene/348 |
| Ensembl ID | ENSG00000130203 |
| UniProt ID | P02649 |
| OMIM ID | 107741 |
| HGNC ID | 613 |
| Aliases | AD2, LDLCQ5, LPG, APO-E, ApoE4 |
Description
APOE (Apolipoprotein E) encodes a major apolipoprotein that mediates lipid transport and metabolism. It is a key component of chylomicrons, VLDL, and HDL particles, facilitating receptor-mediated uptake of lipoproteins in the liver and peripheral tissues. APOE is also involved in neuronal repair, immune regulation, and amyloid-beta clearance in the brain. Three common alleles (ε2, ε3, ε4) define the major isoforms, with ε4 being the strongest genetic risk factor for late-onset Alzheimer's disease and also associated with cardiovascular disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer's disease (late-onset) | APOE ε4 allele increases amyloid-beta aggregation and reduces clearance | OMIM 104300; multiple GWAS and meta-analyses |
| Hyperlipoproteinemia type III | Homozygosity for APOE ε2 (Arg158Cys) impairs LDL receptor binding, causing remnant accumulation | OMIM 107741; ClinVar |
| Cardiovascular disease | APOE ε4 associated with higher LDL cholesterol and atherosclerosis risk | OMIM 107741; large cohort studies |
| Age-related macular degeneration | APOE ε4 may confer protective effect; ε2 associated with increased risk | ClinVar; literature review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 174.2 | High |
| Adipose tissue | 42.1 | Medium |
| Brain (cortex) | 38.5 | Medium |
| Adrenal gland | 35.0 | Medium |
| Kidney | 12.3 | Low |
| Lung | 8.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 152.3 | Hepatocyte line, high expression |
| SH-SY5Y | 45.6 | Neuroblastoma line, moderate expression |
| THP-1 | 28.4 | Monocyte line, moderate expression |
| A549 | 6.2 | Lung epithelial line, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs429358 (Cys130Arg) | missense | ~15% (global) | Defines ε4 allele; increases Alzheimer's risk |
| rs7412 (Arg176Cys) | missense | ~7% (global) | Defines ε2 allele; associated with type III hyperlipoproteinemia when homozygous |
| p.Leu46Pro | missense | <0.1% | Rare variant; possible dominant negative effect on lipid binding |
| p.Glu255Lys | missense | <0.1% | Rare; reported in familial combined hyperlipidemia |
Mutation functional classification
Loss of Function (LOF)
Homozygous APOE ε2 (p.Arg176Cys) reduces LDL receptor binding affinity, leading to impaired clearance of remnant lipoproteins (type III hyperlipoproteinemia).
Gain of Function (GOF)
APOE ε4 (p.Cys130Arg) enhances amyloid-beta aggregation and neuroinflammation, contributing to Alzheimer's disease pathology.
Dominant Negative (DN)
Rare missense variants (e.g., p.Leu46Pro) may interfere with normal APOE dimerization and lipid transport, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005319 – lipid transporter activity | • GO:0008201 – heparin binding |
| • GO:0001540 – amyloid-beta binding | • GO:0005615 – extracellular space |
| • GO:0034364 – high-density lipoprotein particle | • GO:0006629 – lipid metabolic process |
| • GO:0055085 – transmembrane transport |
Pathways
• Alzheimer's disease (KEGG hsa05010)
• Cholesterol metabolism (KEGG hsa04979)
• PPAR signaling pathway (KEGG hsa03320)
• Lipoprotein metabolism (Reactome R-HSA-174824)
Protein Summary
Apolipoprotein E (ApoE) is a 34 kDa secreted glycoprotein composed of 317 amino acids. It contains an N-terminal receptor-binding domain (residues 136-150) and a C-terminal lipid-binding domain. ApoE mediates the clearance of triglyceride-rich lipoproteins via LDL receptor (LDLR) and LRP1. In the brain, ApoE is primarily produced by astrocytes and microglia, and it modulates amyloid-beta aggregation, clearance, and neuroinflammation. The three common isoforms (ApoE2, ApoE3, ApoE4) differ at residues 130 and 176, conferring distinct functional and disease-risk profiles.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| APOE Knockout HEK293 Cell Line | EDJ-KQ172 | Human | 348 | Details Get a Quote |
| APOE Knockout A-549 Cell Line | EDJ-KQ41271 | Human | 348 | Details Get a Quote |
| APOE Knockout HCT 116 Cell Line | EDJ-KQ41272 | Human | 348 | Details Get a Quote |
| APOE Knockout HeLa Cell Line | EDJ-KQ41273 | Human | 348 | Details Get a Quote |
| APOE Knockout LLC-MK2 Cell Line | EDJ-KZ546 | Rhesus Monkey | 348 | Details Get a Quote |
| APOE Knockout Hep-G2 Cell Line | EDC07735 | Human | 348 | Details Get a Quote |
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